Preliminary studies have identified a unique B cell population that constitutively produces IL-27. These B cells are relatively rare in-vivo but we have developed an ex-vivo assay that allows us to produce large amounts of this Breg population. We are now characterizing the immuno-biology of the i27-Breg cells by single-cell RNA-Seq (scRNA-Seq), Chip-Seq and ATAC-Sequencing. We are also investigating regulatory functions of i27-Bregs in the EAU and EAE models. In addition, we have isolated exosomes that contain IL-27 as its major cargo from mouse B cells and used the exosomes to treat uveitis in mice. The IL-27 containing exosomes protected mice from EAU.